It is known that the symptoms of cardiac failure are related to some combination of circulatory volume expansion and reduced cardiac output. Therapy for cardiac failure has commonly involved the administration of an inotropic drug to increase the contractile force of the heart and the administration of a diuretic to increase urinary excretion of salt and water and to reduce left ventricular end diastolic pressure. Inotropic therapy with digitalis theoretically allows a greater stroke output for any given ventricular filling pressure. Objective evidence indicates digitalis may be of limited value in relieving symptoms associated with congestive heart failure. A diuretic may relieve the symptoms of volume expansion, but does not improve left ventricular performance. In the setting of mild congestive heart failure related to chronic coronary-artery disease or to non-ischemic forms of primary myocardial disease, digitalis and diuretic therapy is often effective in relieving digitalis and diuretic therapy is often effective in relieving symptoms of failure and in restoring a nearly normal functional state. However, in more severe degrees of failure, and in a setting of acute cardiac events when low cardiac output predominates, the conventional treatment may be inadequate in interrupting the physiological responses to the reduction in stroke volume. Physiological compensatory responses, while initially tending to restore normal tissue perfusion, also result in elevated peripheral vascular resistance. This elevated resistance to left ventricular outflow cannot be compensated for by the already dispersed left ventricle and cardiac output is even further depressed. Neither digitalis nor diuretics provide sufficient cardiotonic effect to adequately enhance cardiac output, and neither reduces the elevated peripheral vascular resistance.
Some vasodilator drugs which are known to relax the peripheral arteriolar bed have been found to be effective in relieving the signs of both elevated circulatory resistance and low cardiac output. A variety of vasodilator drugs have been employed to treat cardiac failure, both acutely administered intraveneous agents and chronically administered oral agents. The sites of action of these drugs vary so widely that each drug produces a rather distinct pattern of hemodynamic responses. The practical application of these drugs in the management of cardiac failure requires an understanding not only of circulatory effects of individual agents, but also of the physiological effects of various circulatory responses on cardiac and peripheral vascular function. Digitalis, a well known inotropic agent, has been shown to produce a disappointingly small improvement in pump function in a setting of acute myocardial infarctions.
Many vasodilator drugs, such as sodium nitroprusside, nitroglycerin, phentolamine and trimethaphan, have been demonstrated to improve pump functions in patients with left ventricular failure during the acute phase of myocardial infarction. The therapeutic aim of vasodilator drugs is to improve cardiac perfomance by reducing the elevated left ventricular filling pressure and by augmenting cardiac output. Arterial pessure may fall, but the desired hemodynamic effect can usually be achieved with little or no change in pressure. In some cases of severe congestive heart failure, reduction of outflow resistance leads to an increase in stroke volume with little or no change in heart rate. Under these circumstances, cardiac output may increase drastically and blood pressure does not change. In cases where blood pressure falls, an increase in reflex sympathetic nerve activity may cause side effects such as tachycardia, renin secretion and fluid retention which may limit the use of vasodilators.